Selective lung tissue ablation

ABSTRACT

Medical methods and systems are provided for effecting lung volume reduction by selectively ablating segments of lung tissue.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a continuation of U.S. application Ser. No.11/460,860, filed Jul. 28, 2006, now U.S. Pat. No. 7,628,789, whichclaims the benefit of Provisional Application No. 60/709,376, filed Aug.17, 2005, the full disclosures of which are incorporated herein byreference.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates generally to medical methods andapparatus. More particularly, the present invention relates to methodsfor selectively ablating target sites in the lung while protectingadjacent lung and tissue structures.

Chronic obstructive pulmonary disease is a significant medical problemaffecting 16 million people or about 6% of the U.S. population. Specificdiseases in this group include chronic bronchitis and emphysema.Emphysema is a condition of the lung characterized by the abnormalpermanent enlargement of the airspaces distal to the terminalbronchiole, accompanied by the destruction of their walls, and withoutobvious fibrosis. It is known that emphysema and other pulmonarydiseases reduce the ability of one or both lungs to fully expel airduring the exhalation phase of the breathing cycle. One of the effectsof such diseases is that the diseased lung tissue is less elastic thanhealthy lung tissue, which is one factor that prevents full exhalationof air. During breathing, the diseased portion of the lung does notfully recoil due to the emphysematic lung tissue being less elastic thanhealthy tissue. Consequently, the diseased lung tissue exerts arelatively low driving force, which results in the diseased lungexpelling less air volume than a healthy lung. The reduced air volumeexerts less force on the airway, which allows the airway to close beforeall air has been expelled (air trapping), another factor that preventsfull exhalation. While a number of therapeutic interventions are usedand have been proposed, none are completely effective, and chronicobstructive pulmonary disease remains the fourth most common cause ofdeath in the United States. Thus, improved and alternative treatmentsand therapies would be of significant benefit.

Of particular interest to the present invention, lung function inpatients suffering from emphysema and other chronic obstructivepulmonary diseases can be improved by reducing the effective lungvolume, typically by resecting or otherwise isolating diseased portionsof the lung. Resection of diseased portions of the lungs both promotesexpansion of the non-diseased regions of the lung and decreases theportion of inhaled air which goes into the lungs but is unable totransfer oxygen to the blood. Lung reduction is conventionally performedin open chest or thoracoscopic procedures where part of the lung isresected, typically using stapling devices having integral cuttingblades.

While effective in many cases, conventional lung reduction surgery issignificantly traumatic to the patient, even when thoracoscopicprocedures are employed. Such procedures often result in theunintentional removal of healthy lung tissue, and frequently leaveperforations or other discontinuities in the lung which result in airleakage from the remaining lung. Even technically successful procedurescan cause respiratory failure, pneumonia, death, and many older orcompromised patients are not even candidates for these procedures.

The use of devices that intrathoracically isolate a diseased region ofthe lung in order to reduce the volume of the diseased region, such asby collapsing the diseased lung region, has recently been proposed. Forexample, self-expanding plugs, one-way valves, and other occlusiondevices may be implanted in airways feeding a targeted region of thelung to isolate the region of the diseased lung region. However, evenwith the implanted isolation devices properly deployed, air can flowinto the isolated lung region via a collateral pathway. This can resultin the diseased region of the lung still receiving air even though theisolation devices were implanted into the direct pathways to the lung.Collateral flow can be, for example, air flow that flows betweensegments of a lung (intralobar collateral ventilation), or it can be,for example, air flow that flows between lobes of a lung (interlobarcollateral ventilation). Collateral resistance is reduced in emphysema,and may be substantially lower than airway resistance. Fissures areoften incomplete, allowing collateral ventilation to traverse lobes. Itis axiomatic that absorptive atelectasis could not develop in patientsafter the occlusive devices were placed if occluded regions receivedmore ventilation than the rate of gas absorption. Collateral channelswere the only pathways available for such ventilation.

For these reasons, it would be desirable to provide improved methods,apparatus, and systems for treating diseased lung regions. Inparticular, it would be desirable to provide such methods, apparatus,and systems which are capable of treating diseased regions havingcollateral ventilation using principally or only intrabronchial accessroutes. It would be still further desirable if the present inventioncould provide for complete isolation of the diseased lung region whileminimizing or eliminating any risk of injury or trauma to adjacent lungor other tissue structures. At least some of these objectives will bemet by the inventions described hereinbelow.

BRIEF SUMMARY OF THE INVENTION

The present invention provides for improved and alternative methods,apparatus, and systems for the minimally-invasive treatment of diseasedlung regions, such as those which arise from emphysema, bronchitis, orother diseases. The treatments may be performed endobronchially,typically through a transesophageal access route, and provide forsubstantially complete isolation of a target lung region, referred tohereinafter as a “target site,” even when the region or site is subjectto collateral ventilation which would render prior occlusive treatmentprotocols ineffective. Typically, the patients will be screened todetermine if the target site is subject to collateral ventilation priorto performing the method of the present invention.

The target sites within the lung are typically treated by deliveringheat or other energy to raise the temperature of tissue within thetarget site to a level, typically from 40° C. to 95° C., and for a timesufficient to induce complete or substantially complete tissue necrosisfollowed by collapse of the treated site. The energy is preferablydelivered by a catheter or other elongate probe which may betransesophageally and intrabronchially introduced to one or more targetairways within the target site. Typically, the treatment catheters willhave energy-applying structures, such as electrodes, heat exchangers,optical heating elements, or the like, which are sufficiently longand/or conformable to access and fill most or all of the targetairway(s) within the target site being treated. Typically, theenergy-applying elements will have a length in the range from 2 cm to 20cm, preferably from 5 cm to 10 cm.

Optionally, heat-transfer liquids and/or gases may be introduced intothe airways within the target site to enhance heat distribution from theheat-transfer elements. The heat-transfer liquids and/or gases maythemselves be heated and under some circumstances could be the soleenergy-delivering medium used in the methods of the present invention.Further optionally, the temperature can be monitored within thetreatment site to assure that the temperature is maintained in thedesired treatment ranges. For example, electronic temperature sensorscan be located on the catheter or probe within the target site andfeedback control systems can be used to control the rate of energydelivered to maintain the desired temperature.

In a further aspect of the present invention, steps will usually betaken to protect adjacent regions in the lung and external tissuestructures while energy is delivered to the target site. Typically, theentire lung in which the target site is located will be collapsed inorder to isolate the lung tissue from the surrounding thoracic tissuestructures. Usually, while the target lung is collapsed, the otherpatient lung will be actively ventilated both to cool the lung and toprovide oxygen to the patient. In addition to collapsing the treatmentlung, cold heat-transfer liquids or gases may be introduced to the lunglobes, segments, or sub-segments adjacent to the target site which isbeing treated.

Often, before treating a patient with the heating methods of the presentinvention, the target site of the patient will be tested for collateralventilation using any one of a variety of techniques, as described inco-pending applications referenced below. As a result of such screening,patients where the diseased target site is subject to collateralventilation, and who are therefore less likely to be successfullytreated by prior occlusive techniques, may be treated by more rigorousmethods of the present invention.

In a first aspect of the present invention, methods for selectivelyablating a treatment site in a lung comprise advancing a treatmentapparatus through an airway toward the treatment site in the lung.Energy is then delivered through the treatment apparatus to heat tissuewithin the treatment site to a level which destroys the tissue whileprotecting adjacent regions in the lung and surrounding tissue fromthermal damage. The temperature of the tissue within the treatment siteis typically raised to a level in the range from 40° C. to 95° C.,typically from 70° C. to 95° C. The energy may take a variety of forms,including electrical energy, heat energy, light energy, sound energy,radiation from microwaves or radioisotopes, and combinations thereof. Inexemplary embodiments, the delivered energy will be thermal, typicallygenerated by current flow through a resistive coil or delivery of a hotfluid into the lung or, more typically, into a heat exchanger in thetreatment apparatus. In all cases, however, the energy delivery may beenhanced by introduction of an electrically conductive and/orheat-exchange liquid or gas into the treatment site, typically through alumen or other access provided by the treatment apparatus, optionallybetween two or more isolation balloons.

Complete and generally uniform distribution of the heat throughout thevolume of the lung treatment site may be achieved in a variety of ways.In addition to delivering an auxiliary heating exchange medium, thetreatment apparatus may include multiple heat exchange elements orcomponents. For example, the heat exchange apparatus may includemultiple electrodes, coils, heat exchange elements so that they may beplaced in more than one airway within the volume of the treatment site.The multiple heat exchange elements may be included on a singletreatment apparatus or could each be delivered by separate heat-transferapparatus, such as separate catheters, probes, or the like.

While the energy is being delivered to the treatment site for raisingthe tissue temperture therein, measures will be taken to protectadjacent regions within the lung and within the surrounding thoraciccavity. Usually, the lung which comprises the treatment site will becollapsed to provide for physical spacing between the lung tissue andthe upper thoracic cavity. For example, the lung may be punctured fromthe inside, preferably from a location within the treatment site, tocreate a pneumothorax to separate the lung from the chest wall. Thepuncture can then be sealed, optionally as part of the ablation of thetreatment site, although use of an occlusal stent or other sealing plugmay also be needed. In addition, the adjacent regions which are notbeing treated that are within the lung which is being treated, willfurther be treated, typically by circulating a cooling liquid, gas, orother medium to keep the temperature below the level associated withnecrosis or thermal damage.

In a second aspect of the present invention, treatment apparatus forablating a treatment site in a lung of a patient comprises a shafthaving a proximal end and a distal end. An energy-emitting element maybe disposed near the distal end of the shaft, where the energy-emittingelement is configured to extend through and conform to an airway withinthe treatment site of the lung. In the exemplary embodiments, theenergy-emitting element will comprise an elongate member which willextend through the target site in the lung, typically having a length inthe range set forth above. The energy-emitting element may be, forexample, an elongate coil-shaped electrode, an elongate, braided wireelectrode, or the like. In all cases, the energy-emitting element mayfurther include an expansion element which permits the energy-emittingelement to be expanded to conform to a shape of the airway of thetreatment site. For example, the expansion element may comprise aninflatable balloon, or may comprise a constraint which can be releasedto allow expansion of a self-expanding energy-emitting element.Optionally, the treatment apparatus may further comprise catheters fordelivering electrically conductive and/or thermally conductive liquids,gels, or other fluids into the treatment site. Often the treatmentapparatus will further include one or more isolation balloons forconducting the fluids to desired regions within the treatment site.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an embodiment of a double lumen tube advanced intothe dependent lung.

FIGS. 2A-2B illustrate example double lumen tubes.

FIGS. 3A-3B illustrate example endobronchial tubes.

FIG. 3C illustrates the endobronchial tube of FIGS. 3A-3B positioned inthe anatomy with a treatment apparatus.

FIGS. 4-5 illustrate isolation/aspiration procedures.

FIGS. 6A-6B, 7, and 8A-8B illustrate embodiments of treatmentapparatuses.

FIG. 9 illustrates the use of isolation balloons for containing anelectrical or thermal conduction fluid within a treatment site.

DETAILED DESCRIPTION OF THE INVENTION

The methods, apparatus, and systems of the present invention are usedfor delivering energy to diseased target sites within a patient lung forablation and consequent isolation of the diseased segment to treatdiseased lung regions resulting from emphysema, bronchitis, and otherprimary diseases. The treatment methods of the present invention aremore rigorous than and intended as alternatives to the intrabronchialocclusion methods described previously for isolating diseased regionswithin a patient's lung. The methods of the present invention will bereferred to generally hereinbelow as selective lung tissue ablation(SLTA).

Prior to treatment with the SLTA methods of the present invention,patients will usually be tested with a collateral ventilation (CV) testalong with a segmental diagnostic test, such as described in U.S. patentapplication Ser. No. 11/296,951; and U.S. patent application Ser. No.10/241,733, both incorporated herein by reference for all purposes.Patients who test negative for the collateral ventilation test couldprobably benefit from the less traumatic endobronchial volume reductiontreatment, which relies on placing occlusal stents in their target lungregions (U.S. Pat. No. 6,287,290). Patients who test positive for the CVmeasurements could be considered for the more invasive SLTA treatmentprocedure described herein. However, it should be appreciated thatpatients may receive the SLTA treatment based on a variety of reasonsand will not necessarily undergo CV testing prior to receiving SLTAtreatment.

The SLTA methods of the present invention may be used particularly for atreatment site in a lung that is supplied air through one or morecollateral pathways. Such ablation may be desired to induce collapse inthe lung region. In accordance with one aspect of the invention, thereis disclosed a method of inducing one lung ventilation (OLV) in theemphysematous patient. This may be achieved with the use of a variety ofdevices. For example, FIG. 1 illustrates an embodiment of a double lumentube 10 (such as manufactured by Mallinkcrodt Corp.) advanced into thedependent lung DL. Double lumen tube 10 in the formula Carlens tube areillustrated in FIGS. 2A-2B. FIG. 2B illustrates the Carlens tube of FIG.2A inserted in a body lumen at a bifurcation, as it would be placed inthe tracheal-bronchial tree.

OLV could also be introduced by other methods, such as with the use ofan endobronchial blocker catheter. Or, with the use of a smallerdiameter endobronchial tube 20, such as illustrated in FIGS. 3A-3B. Theendobronchial tube may have, for example, a 6 mm ID and be shapedsimilarly to an endotracheal tube (C shaped to follow the curvature ofthe upper airway, but also would have a right or left sided curve forselective cannulation of the main stem bronchus). An isolation cuff 22may have in general shape and pressure/volume characteristics which aresimilar to an endotracheal tube, however the cuff diameter would besmaller to accommodate the smaller size of the mainstem bronchus. Thisdesign would allow the bronchoscopist to advance any treatment apparatusalongside the tube while providing the necessary OLV procedure, asillustrated in FIG. 3C.

The left side of the lung (dependent lung DL) can thus be isolated andventilated from the right side of the lung (nondependent lung NL). Bypuncturing the chest wall with a needle placed percutaneously, thenondependent lung NL can be collapsed. Alternatively, the puncture couldbe created from inside the inside of the lung, preferably through thewall adjacent to the treatment site that will be sealed during ablation.This separates the target lung region(s) from the chest wall which isintended to minimize thermal damage which may be caused by the ablationprocess.

Since emphysematous or other diseased lung tissue may not collapseeasily on it's own, an isolation/aspiration procedure may optionally beperformed to collapse the target lung region as much as possible. If,for example, the right upper lobe is diseased, an isolation sheath 30may be introduced over a bronchoscope (as described in U.S. Pat. No.6,585,639 incorporated herein by reference for all purposes) to isolatethe target site (lobe or segment). An additional balloon tippedisolation catheter 32 may be introduced alongside of thesheath/bronchoscope device. The balloon 34 would be positioned the way,that the feeding bronchus to the RML (right middle lobe) and RLL (rightlower lobe) both would get occluded. This would close airflow to the RMLand RLL, and would prevent collateral channels to backfill the targetRUL, thus enhance the collapse of the target lung area. Both of thesedevices may be introduced, for example, either via a double lumen tubeor alongside of an endobronchial tube. After inflating the balloons, anaspiration device may be connected to the working channel of thebronchoscope to facilitate the collapse of the target lung region. Thetarget lung region is thus collapsed as much as possible, as illustratedin FIG. 4 (expiration) and FIG. 5 (inspiration). A treatment apparatusmay then be positioned at the treatment site.

Exemplary treatment apparatuses include a balloon tipped catheter,illustrated in FIGS. 6A-6B, a coil tipped catheter, illustrated in FIG.7, and a braided wire electrode catheter, illustrated in FIGS. 8A-8B.The balloon-tipped catheter 40 comprises an inflatable balloon 42 orother radially expandable structure having a plurality of electrodes 44on its outer surface. Inflation of a balloon within an airway of thetarget site of the lung can thus engage the multiple electrodes againstthe wall of the airway in order to deliver radiofrequency or otherenergy, as discussed below. The catheter 50 includes a radiallyexpandably coil-shaped electrode 52 which is flexible and able toconform to the shape and size of the airway in which it is deployed. Thecatheter 60 carries a self-expanding braided wire electrode structure 62which is carried in its non-expanded configuration while the catheter 60is delivered to its target site within the lung. The electrode structuremay then be released from constraint, for example, using a release wire64 which is threaded through the braided electrode. Alternatively, thebraided wire electrode structure 62 may be covered with a sheath (notshown) or other restraining structure which may be pulled back torelease the sheath so that it can self-expand. In either case, thebraided electrode structure can assume an expanded configuration whichconforms to the inner wall of the airway A, as shown in FIG. 8B. In allcases, it may be desirable to introduce a conductive gel through thetreatment site to enhance electrical conduction. The gel could beintroduced on or by the treatment catheters or by other catheters orprobes.

The treatment apparatus is positioned at the treatment site (for exampleone placed in segment B1 and an other placed in B2 of FIG. 1), and abipolar RF generator may be activated to provide suitable radiofrequency(RF) energy, preferably at a selected frequency in the range of 10 MHzto 1000 MHz. The emitted energy is converted within the tissue into heatin the range of about 40° C. to about 95° C. As the temperatureincreases, it is believed that the collagen undergoes a structuraltransformation whereby the collagen fibers contract and new cross linksare formed. If a full lobar ablation is needed, two, three, or moreelectrode catheters could be placed and either monopolar or bipolar RFenergy could be used.

Selective thermal ablation of the lung tissue is believed to cause thecollagen matrix to shrink, thereby reducing the size of the target lungsegment as well as closing up the collateral channels to preventreinflation. Deleterious effects in the cells making up the tissue beginto occur at about 42° C. As the temperature of the tissue increasesbecause of the heat generated by the tissue's resistance, the tissuewill undergo profound changes and eventually, as the temperature becomeshigh enough, that is, generally greater than 45° C., the cells will die.The change of tissue resistance or impedance could be monitored and usedfor controlling the depth of ablation. The zone of cell death is knownas a lesion and the procedure followed to create the lesion is commonlycalled an ablation. As the temperature increases beyond cell deathtemperature, complete disintegration of the cell walls and cells causedby boiling off of the tissue's water can occur. Cell death temperaturescan vary somewhat with the type of tissue to which the power is beingapplied, but generally will begin to occur within the range of 45° C. to60° C., though actual cell death of certain tissue cells may occur at ahigher temperature. Optionally, polymerizing gels can be introduced tothe treatment site to promote collagen cross-linking and lung volumereduction.

In addition to RF energy, other forms of energy including alternatingelectrical current, microwave, ultrasound, and optical, such as coherent(e.g., laser) or incoherent (e.g., light emitting diode or tungstenfilament), can be used, as well as thermal energy generated from anelectrically resistive coil, a hot fluid element (e.g., circulatingliquids, gases, combinations of liquids and gases, etc.), radioisotopes,and the like. Thermal energy also includes the use of cold media (cryoablation). The hot fluid element may comprise, for example, an elongatedmember that includes a conduit system whereby heated fluid istransported through the center of the member and then channeled outwardtoward the inner surface of the member. In one embodiment the heatedfluid is diverted to contact the inner surface of the elongated memberso that energy radiates from selected areas on the outer surface of themember corresponding to areas. Regardless of the source, energydelivered to the target lung tissue should be such that only theselected lung regions are ablated, while they are away from the chestwall to minimize thermal damage. Optionally, tissue contraction andvolume reduction can be enhanced by immediately cooling a heat-ablatedtreatment site. For example, liquid nitrogen can be introduced followingablation to induce permanent cross-linking of the collagen.

Neighboring lobes or segments can be ventilated or just pressurized by acooler gas or liquid to minimize thermal damage to them as well. Theisolation catheter 32 of FIG. 3C may be used to deliver cooling media toneighboring lobes, segments, or subsegments of the lung being treated.The balloon 34 tipped isolation catheter 30 would be introducedalongside of the treatment catheter 30. The balloon would be positionedin a manner so that the feeding bronchus to the RML (right middle lobe)and RLL (right lower lobe) both would be occluded. Both of thesecatheters would be introduced either via the double lumen tube oralongside of the EB tube. Treatment can be done on only one segment or aplurality of segments at once. The cooling media can be any gas orliquid, for example cooled air, cooled oxygen, or a cooled liquid, suchas saline or perfluorocarbon, etc. By controlling the pressure andtemperature simultaneously between the target lung region versus theneighboring lung tissue, selective lung tissue ablation can be achievedwith minimal thermal damage to the non-targeted sites.

A conductive liquid such as isotonic or hypertonic saline could also beintroduced into a lobe or a segment. Air would be desirable to beremoved prior to instilling the liquid. An electrode pad may be placedunder the patient's chest to provide grounding. Once the liquid is inplace, an electrode or plurality of electrodes would be inserted intothe proximal end of the liquid pathway to communicate electrically withthe instilled conductive liquid. A monopolar RF source could beactivated to cause the liquid to heat up to a specific temperature.

Referring now to FIG. 9, a treatment site TS in the right upper lung isisolated with a balloon catheter 100 having an isolation balloon 102 atits distal end. The right lower lung is isolated with a second ballooncatheter 110 having an isolation balloon 112 at its lower end. A pair ofsecondary balloon catheters 120, 122 having isolation balloons 124, 126is introduced through a central lumen of the catheter 100. The isolationballoons 124, 126 are advanced into selected airways and inflated tocreate an isolated region between the balloon 102 and the more distalisolation balloons 124 and 126. It will be appreciated that in someinstances only a single secondary isolation balloon would be used, whilein other instances, three or more secondary isolation balloons could beused. In all cases, an electrically or thermally conductive fluid isintroduced through the catheter 100 into the isolated region createdbetween the isolation balloons 102, 124, and 126. Energy can betransferred with the treatment site TS by delivering energy into thefluid, or optionally cooling the fluid to remove energy from thetreatment site. In the case of electrically conductive fluids,radiofrequency or other energy may be introduced into the fluid fromcatheter 100, where the energy will be conducted throughout theelectrically conductive fluid to treat the tissue. Alternatively,electrodes could be provided on the catheters 120 and 122. Still furtheralternatively, heating elements could be placed on the catheters 120 and122, or elsewhere within the system in order to heat thermallyconductive fluids.

Other alternative treatment is possible for closing up collateralchannels: same One Lung Ventilation (OLV) technique combined with VideoAssisted Thoracoscopic Surgery (VATS) and mechanically by clipping orusing an RF based cut and seal device to separate the incompletefissures between lobes. After that either EVR could be performed byplacing the occlusal stents or thermal ablation would be required.

While the above is a complete description of the preferred embodimentsof the invention, various alternatives, modifications, and equivalentsmay be used. Therefore, the above description should not be taken aslimiting the scope of the invention which is defined by the appendedclaims.

What is claimed is:
 1. A method for selectively ablating a treatment region in a lung comprising: advancing a treatment apparatus through an airway toward the treatment region in the lung; and exchanging energy through the treatment apparatus to heat or cool the treatment region to a level which destroys tissue at the region; and protecting adjacent regions in the lung and surrounding tissue from thermal damage by controlling pressure and temperature simultaneously at the treatment region and at one or more untreated regions adjacent the treatment region so that thermal damage to the untreated regions is minimized, wherein the exchanged energy induces tissue necrosis followed by the collapse of the treatment region.
 2. A method as in claim 1, where exchanging energy heats tissue to a temperature in the range from 40′C to 95° C.
 3. A method as in claim 1, wherein the exchanged energy comprises radio frequency, alternating current, microwave, ultrasound, coherent light, incoherent light, radioisotopes, or any combination of these.
 4. A method as in claim 1, wherein the exchanged energy comprises thermal energy generated from a resistive coil or a hot fluid element.
 5. A method as in claim 1, wherein the treatment region comprises a lobe or segment of the lung.
 6. A method as in claim 5, wherein the untreated regions adjacent the treatment region comprises an adjacent lobe or segment of the lung.
 7. A method as in claim 1, wherein protecting adjacent regions comprises ventilating or pressurizing the adjacent region with a cooler gas or liquid.
 8. A method as in claim 7, wherein the cooler gas or liquid comprises cooled air cooled oxygen, cooled saline, or a cooled perfluorocarbon.
 9. A method as in claim 7, wherein the cooler gas is delivered via the treatment apparatus. 